markers of anthracycline-related cardiac muscle injury

Conditions: Osteosarcoma; Ewing's Sarcoma Family of Tumors; Rhabdomyosarcoma; Non-rhabdomyosarcoma Soft Tissue Sarcomas

Summary: anthracycline antibiotics are included in the chemotherapy regimens of approximately 82% of patients with bone cancer and 44% of those with soft tissue sarcoma diagnosed in childhood or adolescence. impaired cardiac function occurs after treatment with anthracyclines. the frequency of impairment increases with increasing cumulative dose. there are inadequate data regarding the relationship between doxorubicin administration and changes in serum levels of cardiac troponin t (ctn-t) or i (ctn-i), n-terminal (nt) brain natriuretic peptide (bnp), or tissue doppler imaging parameters. this non-therapeutic study proposes a prospective, single arm study of serial changes in tissue doppler imaging parameters, ctn-t and nt-bnp in children and adolescents with malignant bone and soft tissue tumors whose planned chemotherapy includes treatment with ≥ 375 mg/m2 of doxorubicin. the proposed study will rigorously evaluate the usefulness of serial determinations of tissue doppler imaging, ctn-t and nt-bnp for very early identification of anthracycline-related myocardial injury. demonstration that one or more of these markers identifies subclinical myocardial damage and that biomarker or tissue doppler imaging parameters exhibit a dose-response relationship with cumulative doxorubicin dose would facilitate intervention trials in patients at risk for anthracycline cardiomyopathy.

the primary aim of this proposal is to serially evaluate imaging tests in previously untreated patients with osteosarcoma, ewing's sarcoma family of tumors(esft), rhabdomyosarcoma and intermediate and high-risk non-rhabdomyosarcoma soft tissue sarcomas whose planned treatment includes a cumulative doxorubicin dose ≥ 375 mg/m2 to determine if serial levels of one or more of these potential markers of cardiac muscle injury obtained prior to each infusion of doxorubicin and at the completion of chemotherapy correlate with increasing cumulative anthracycline exposure. the secondary aim of the study is to estimate the proportion of patients with decreased (evaluation j - evaluation j+1) peak longitudinal systolic strain (ε) or strain rate (sr), peak radial systolic ε or sr, peak radial systolic myocardial velocity or peak longitudinal systolic myocardial velocity among those who have a shortening fraction (sf) ≥ 29% prior to each infusion of anthracycline. this study will evaluate whether the serum levels of ctn-t and/or nt-bnp will increase following doxorubicin administration. the study will evaluate whether the serum levels of ctn-t and/or nt-bnp will increase with increasing cumulative doxorubicin dose.

Eligibility criteria:
inclusion criteria: * between 0 and 21 years of age * diagnosis of osteosarcoma, ewing sarcoma family of tumors, rhabdomyosarcoma, or intermediate or high-risk non-rhabdomyosarcoma soft tissue sarcoma * planned treatment includes administration of a cumulative anthracycline dose ≥ 375 mg/m2 exclusion criteria: * pregnant females * patients with a history of cancer prior to the current malignancy * patients whose treatment will include radiation therapy to a volume that will include the heart

Keywords: anthracycline cardiac muscle injury doxorubicin doppler imaging intermediate non-rhabdomyosarcoma soft tissue sarcomas high-risk non-rhabdomyosarcoma soft tissue sarcomas